MelanomaPhase 1NCT01456104
Immune Responses to Autologous Langerhans-type Dendritic Cells Electroporated With mRNA Encoding a Tumor-associated Antigen in Patients With Malignancy: A Single-arm Phase I Trial in Melanoma
A Phase 1 study testing Langerhans-type dendritic cells (a.k.a. Langerhans cells or LCs) in people with Melanoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
This study is being done to see if the investigators can help the immune system to work against melanoma. A dendritic cell is another type of white blood cell. It has most, if not all, of the proteins needed to make T cells work to destroy cancer cells. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Melanoma
- What is being tested?
- Langerhans-type dendritic cells (a.k.a. Langerhans cells or LCs)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Oct 2011to 12 Jan 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of melanoma, AJCC stage IIB, IIC, III, or IV (MIa), with histologic confirmation by the Department of Pathology at MSKCC.
- Patients must be HLA-A*0201 positive, based on high resolution DNA level typing.
- Expected survival of greater than 3 months.
- Karnofsky performance status of 70 or higher
- All patients should have undergone surgical treatment appropriate to their stage of disease
- Patients may not have received chemotherapy, immunotherapy, or radiation within a minimum of 28 days (minimum of 42 days for nitrosoureas or mitomycin) before participation in this protocol.
Who cannot join
- Pregnant or lactating women because of unknown risks to the fetus or infant.
- Patients requiring systemic corticosteroids or comparable exogenous immunosuppressive agent(s) (no exclusion for use of NSAIDs).
- Patients with a known immunodeficiency (e.g., infection with HTLV-1,2, HIV-1,2; etc.).
- Patients with coexisting autoimmune diseases, except vitiligo.
- Patients with baseline impairments of hematologic, hepatic, or renal function (CTCAE v4.0 > grade 1, ANC < 1500, hgb < 10.0 g/dl, plts < 75,000/ul, AST > 3x ULN, creatinine > 1.5xULN), all assessed within four weeks of study entry.
- Patients with organ allografts.
- Patients who are status post splenectomy or status post splenic irradiation.
- Patients with a history of documented pre-existing retinal/choroidal disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
This study is being done to see if the investigators can help the immune system to work against melanoma.
A dendritic cell is another type of white blood cell. It has most, if not all, of the proteins needed to make T cells work to destroy cancer cells. However, dendritic cells do not normally have the cancer proteins on their surface. The challenge then is to combine the antigens with dendritic cells to make a vaccine. The investigators think that the body's T cells might then react against the tumor and help destroy it.
Read more
This study will see if altered dendritic cells will make T cells work against tumor cells. The dendritic cells will be made in a lab and will carry the antigens. These cells then will be injected under the skin.
In this study, the investigators are trying to help the body make a stronger immune response against the cancer. The patient will get the same kind of dendritic cell vaccine used in the earlier study, but with one major difference. The dendritic cells will contain messenger-RNA (mRNA). Cells use mRNA to make proteins. The mRNA will be put into dendritic cells by a laboratory method called electroporation. The mRNA is never given to the patient directly. This mRNA will help the dendritic cell make a tumor antigen like what the cancer expresses. The dendritic cell can then put this tumor antigen on its surface so that the body could make a stronger immune response against the tumor.
- Conditions
- Melanoma
- Being tested
- Langerhans-type dendritic cells (a.k.a. Langerhans cells or LCs)
- Keywords
- vaccine, stage IIB, stage IIC, stage III, stage IV (MIa), Langerhans-type dendritic cells, Immune Responses, 10-229
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Langerhans-type dendritic cells (a.k.a. Langerhans cells or LCs)Biological
Patients will receive a total of 5 vaccinations, comprising a primary immunization followed by four boosters at 3 week intervals with a window of ± 4 days. Vaccines will be dosed at 10x106 LCs per vaccine x 5.
| Study group | Role | What they receive |
|---|---|---|
| vaccine | Experimental | This is a single-arm phase I trial in patients with AJCC stage IIB, IIC, III, and IV (MIa) melanoma in which autologous human Langerhans-type dendritic cells (CD34+hematopoietic progenitor cell (HPC)-derived Langerhans cells, or LCs) will be electroporated with mRNA encoding full-length murine tyrosinase-related peptide 2 (TRP2). LCs will also be loaded with control antigens (HLA-A*0201-restricted flu matrix peptide). Receives: Biological: Langerhans-type dendritic cells (a.k.a. Langerhans cells or LCs) |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety
Toxicity will be graded according to standard NCI/CTEP toxicity criteria. This protocol will use the Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Measured: 1 year
toxicity
Toxicity will be graded according to standard NCI/CTEP toxicity criteria. This protocol will use the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Due to the nature of this treatment and the expected mild erythema and occasional pruritus, only grade 3-4 toxicities will be evaluated
Measured: 1 year
Secondary outcomes (1)
immunogenicity
For this study, the vaccine is considered promising if more than four out of the nine patients have an immunologic response (e.g., tetramer staining and intracellular cytokine secretion assays). Samples taken after vaccination will be considered positive for response if they are higher than the pre-vaccination values by at least two standard deviations. For each patient, the standard deviation of the background (calculated using triplicates) will be computed, and a positive will be defined as greater than two times this value.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2011 (estimated)
- Study start17 Oct 2011
- Primary completion12 Jan 2023
- Study completion12 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Rockefeller University
- Responsible party
- Sponsor
- Investigators
- James Young, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01456104
- Sponsor's protocol ID
- 10-229
- Status last verified
- Jan 2023
- First submitted
- 18 Oct 2011
- Last updated
- 13 Jan 2023
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Responses to Autologous Langerhans-type Dendritic Cells Electroporated With mRNA Encoding a Tumor-associated Antigen in Patients With Malignancy: A Single-arm Phase I Trial in Melanoma
- ClinicalTrials.gov ID
- NCT01456104
- Acronym / sponsor ID
- 10-229
- Conditions
- Melanoma
- Keywords
- vaccine, stage IIB, stage IIC, stage III, stage IV (MIa), Langerhans-type dendritic cells, Immune Responses, 10-229
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Rockefeller University
- Study start
- 17 Oct 2011 (actual)
- Primary completion
- 12 Jan 2023 (actual)
- Study completion
- 12 Jan 2023 (actual)
- First posted
- 20 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being done to see if the investigators can help the immune system to work against melanoma.
A dendritic cell is another type of white blood cell. It has most, if not all, of the proteins needed to make T cells work to destroy cancer cells. However, dendritic cells do not normally have the cancer proteins on their surface. The challenge then is to combine the antigens with dendritic cells to make a vaccine. The investigators think that the body's T cells might then react against the tumor and help destroy it.
This study will see if altered dendritic cells will make T cells work against tumor cells. The dendritic cells will be made in a lab and will carry the antigens. These cells then will be injected under the skin.
In this study, the investigators are trying to help the body make a stronger immune response against the cancer. The patient will get the same kind of dendritic cell vaccine used in the earlier study, but with one major difference. The dendritic cells will contain messenger-RNA (mRNA). Cells use mRNA to make proteins. The mRNA will be put into dendritic cells by a laboratory method called electroporation. The mRNA is never given to the patient directly. This mRNA will help the dendritic cell make a tumor antigen like what the cancer expresses. The dendritic cell can then put this tumor antigen on its surface so that the body could make a stronger immune response against the tumor.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| vaccine | Experimental | Biological: Langerhans-type dendritic cells (a.k.a. Langerhans cells or LCs)This is a single-arm phase I trial in patients with AJCC stage IIB, IIC, III, and IV (MIa) melanoma in which autologous human Langerhans-type dendritic cells (CD34+hematopoietic progenitor cell (HPC)-derived Langerhans cells, or LCs) will be electroporated with mRNA encoding full-length murine tyrosinase-related peptide 2 (TRP2). LCs will also be loaded with control antigens (HLA-A*0201-restricted flu matrix peptide). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of melanoma, AJCC stage IIB, IIC, III, or IV (MIa), with histologic confirmation by the Department of Pathology at MSKCC.
- Patients must be HLA-A*0201 positive, based on high resolution DNA level typing.
- Expected survival of greater than 3 months.
- Karnofsky performance status of 70 or higher
- All patients should have undergone surgical treatment appropriate to their stage of disease
Key exclusion criteria (8 listed)
- Pregnant or lactating women because of unknown risks to the fetus or infant.
- Patients requiring systemic corticosteroids or comparable exogenous immunosuppressive agent(s) (no exclusion for use of NSAIDs).
- Patients with a known immunodeficiency (e.g., infection with HTLV-1,2, HIV-1,2; etc.).
- Patients with coexisting autoimmune diseases, except vitiligo.
- Patients with baseline impairments of hematologic, hepatic, or renal function (CTCAE v4.0 > grade 1, ANC < 1500, hgb < 10.0 g/dl, plts < 75,000/ul, AST > 3x ULN, creatinine > 1.5xULN), all assessed within four weeks of study entry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Langerhans-type dendritic cells (a.k.a. Langerhans cells or LCs)Patients will receive a total of 5 vaccinations, comprising a primary immunization followed by four boosters at 3 week intervals with a window of ± 4 days. Vaccines will be dosed at 10x106 LCs per vaccine x 5. | Biological | vaccine |
Primary outcome
safety
Time frame: 1 year
Toxicity will be graded according to standard NCI/CTEP toxicity criteria. This protocol will use the Common Terminology Criteria for Adverse Events (CTCAE) v4.0
toxicity
Time frame: 1 year
Toxicity will be graded according to standard NCI/CTEP toxicity criteria. This protocol will use the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Due to the nature of this treatment and the expected mild erythema and occasional pruritus, only grade 3-4 toxicities will be evaluated
1 secondary outcome
immunogenicity
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2023.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Young, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Langerhans-type dendritic cells (a.k.a. Langerhans cells or LCs) in people with Melanoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2023.